Session-Specific Effects on Suicidality in Group Therapy: No Evidence for Contagion.

OBJECTIVE: Explicitly addressing suicidality in group therapy is often avoided due to the fear of contagion effects. However, there is some evidence that this fear is not valid. Therefore, the present study aims at contributing to this question by investigating the session-specific effects of two modules on suicidality that are part of the Metacognitive Training for Depression (D-MCT/S). METHODS: Forty-four patients with depression participated in the two modules on suicidality of the D-MCT/S. Before and after each group session, patients filled out a questionnaire asking for symptoms of suicidality, associated cognitions (e.g., hopelessness), and associated emotions (e.g., anger). Data were analyzed by linear mixed-effect models. RESULTS: Approximately 84% of the patients had experienced lifetime suicidal ideation. No within- or between-session effects were found for the modules on suicidality. Sample size was large enough to find small to medium effects (within-session analyses) and medium to large effects (between-session analyses). CONCLUSION: The modules on suicidality did not specifically change suicidal symptoms or associated cognitions and emotions immediately or by the next session. Most importantly, our results disconfirm evidence on deterioration when suicidality is addressed in a highly structured group setting. Whether the current findings also apply to other forms of group therapies needs to be investigated in future studies. HIGHLIGHTSSession-specific investigations allow a thoroughly examination of an interventionMetacognitive Training for Depression showed no contagion effect on suicidality.

Chronic pain in osteoarthritis of the hip is associated with selective cognitive impairment.

INTRODUCTION: Chronic pain of various origin is known to be associated with selective cognitive impairment. Osteoarthritis (OA) of the hip is one of the leading causes of chronic pain in the adult population, but its association with cognitive performance has not been evaluated. Here, we investigate the effect of chronic pain due to unilateral OA of one hip and no further source of chronic pain on cognitive performance. MATERIALS AND METHODS: A neuropsychological test battery, consisting of the Mini-Mental State Examination, Rey-Osterrieth complex figure test, Rivermead behavioural memory test, d2 test of attention, and F-A-S test was applied in 148 patients and 82 healthy pain-free control individuals. The influence of potentially confounding factors such as depression and anxiety was examined. RESULTS: Patients with OA of the hip showed decreased performance in specific neuropsychological tests. Performance in verbal and visual short-term and long-term memory and selective attention tests was significantly poorer compared to healthy controls. Whereas the executive functions "updating", "set shifting", "response inhibition" and "reflection" appear intact, "problem solving" and "planning" were impaired. None of the confounders showed any influence on cognitive performance in both study groups. CONCLUSION: We conclude that chronic pain secondary to end-stage hip OA is associated with selective cognitive impairment. Future studies are required to investigate the effect of total hip arthroplasty on cognitive performance.

Efficacy of metacognitive training for depression as add-on intervention for patients with depression in acute intensive psychiatric inpatient care: A randomized controlled trial.

BACKGROUND: Metacognitive training for depression (D-MCT) is a novel low-intensity group training for economic treatment of depression. Previous studies demonstrate its efficacy in moderately depressed outpatients. The present study evaluated efficacy and patients' perspective of the D-MCT in severely depressed psychiatric inpatients. METHODS: In a randomized-controlled trial, 75 individuals with a major depressive disorder (MDD) were allocated to D-MCT versus euthymic therapy as add-on (twice a week) to cognitive-behavioural-based (CBT) inpatient-care. Depressive symptoms (HDRS, BDI), dysfunctional (meta)cognition (DAS, MCQ-30) and subjective appraisal were assessed at baseline, 4 weeks (post) and 3 months (follow-up). RESULTS: Participants in both conditions showed a large decline in depression at post and follow-up-assessment. No superior add-effect of D-MCT versus active control emerged for depression severity on top of the inpatient care. However, among patients with a diagnosis of MDD with no (vs. at least one) comorbidity, D-MCT participants showed a larger decline in depressive (meta-)cognition at follow-up with medium-to-large effect sizes. D-MCT was evaluated as superior in overall appraisal, treatment preference, motivation and satisfaction. LIMITATIONS: The follow-up time interval of 3 months may have been too short to detect long-term effects. There is emerging evidence that modification of (meta)cognition unfolds its full effects only with time. Effects of CBT inpatient-care on outcome parameters cannot be differentiated. CONCLUSIONS: Although D-MCT as an add-on was not superior in complete case analyses, results suggest greater benefit for patients with MDD and no comorbidity. D-MCT proved feasible in acute-psychiatric inpatient-care and was highly accepted by patients. Future studies should investigate the role of modified (meta)cognition on long-term treatment outcome, including dropout and relapse rates.

Mid-term improvement of cognitive performance after total hip arthroplasty in patients with osteoarthritis of the hip : a prospective cohort study.

AIMS: The aim of this study was to determine whether total hip arthroplasty (THA) for chronic hip pain due to unilateral primary osteoarthritis (OA) has a beneficial effect on cognitive performance. METHODS: A prospective cohort study was conducted with 101 patients with end-stage hip OA scheduled for THA (mean age 67.4 years (SD 9.5), 51.5% female (n = 52)). Patients were assessed at baseline as well as after three and months. Primary outcome was cognitive performance measured by d2 Test of Attention at six months, Trail Making Test (TMT), FAS-test, Rivermead Behavioural Memory Test (RBMT; story recall subtest), and Rey-Osterrieth Complex Figure Test (ROCF). The improvement of cognitive performance was analyzed using repeated measures analysis of variance. RESULTS: At six months, there was significant improvement in attention, working speed and concentration (d2-test; p < 0.001), visual construction and visual memory (ROCF; p < 0.001), semantic memory (FAS-test; p = 0.009), verbal episodic memory (RBMT; immediate recall p = 0.023, delayed recall p = 0.026), as well as pain (p < 0.001) with small to large effect sizes. Attention, concentration, and visual as well as verbal episodic memory improved significantly with medium effect sizes over η2 partial = 0.06. In these cognitive domains the within-group difference exceeded the minimum clinically important difference. CONCLUSION: THA is associated with clinically relevant postoperative improvement in the cognitive functions of attention, concentration, and memory. These data support the concept of a broad interaction of arthroplasty with central nervous system function. Cite this article: Bone Joint J 2022;104-B(3):331-340.

Do implicit measures improve suicide risk prediction? An 18-month prospective study using different tasks.

BACKGROUND: There is accumulating evidence that implicit measures improve the prediction of suicidality within a 6-month follow-up period in psychiatric populations. Building upon these results, we set out to expand the follow-up period and to investigate various implicit methods. METHODS: Seventy-nine inpatients completed the Beck Scale for Suicidal Ideation (BSS) and a range of implicit measures: three implicit association tests (IATs: Death; Self-harm-Me/Others; Self-Harm-Good/Bad) and a subliminal priming task (with separate scores for negative and positive adjectives, each indicating the association between the primes "dying" and "growing"). After 18 months, we reached n = 52 patients and reassessed suicidal ideation, plans, and attempts. RESULTS: In a hierarchical regression, the five implicit task indices were entered after the patient's age, gender, and BSS score at baseline. The implicit scores improved prediction of BSS scores after 18 months compared to prediction based on age, gender, and BSS score at baseline alone. However, none of the implicit measures was associated with suicide plans or attempts during the follow-up period. CONCLUSION: Results suggest that implicit measures can be a useful assessment tool for the prediction of suicidal ideation, even beyond the BSS. However, long-term prediction of suicide plans or attempts using implicit measures seems limited.

Effect of intravenous alteplase on post-stroke depression in the WAKE UP trial.

BACKGROUND AND PURPOSE: The aim was to study the effect of intravenous alteplase on the development of post-stroke depression (PSD) in acute stroke patients, and to identify predictors of PSD. METHODS: This post hoc analysis included patients with unknown onset stroke randomized to treatment with alteplase or placebo in the WAKE-UP trial (ClinicalTrials.gov number, NCT01525290), in whom a composite end-point of PSD was defined as a Beck Depression Inventory ≥10, medication with an antidepressant, or depression recorded as an adverse event. Multiple logistic regression was used to identify predictors of PSD at 90 days. Structural equation modelling was applied to assess the indirect effect of thrombolysis on PSD mediated by the modified Rankin Scale. RESULTS: Information on the composite end-point was available for 438 of 503 randomized patients. PSD was present in 96 of 224 (42.9%) patients in the alteplase group and 115 of 214 (53.7%) in the placebo group (odds ratio 0.63; 95% confidence interval 0.43-0.94; p = 0.022; adjusted for age and National Institutes of Health Stroke Scale at baseline). Prognostic factors associated with PSD included baseline medication with antidepressants, higher lesion volume, history of depression and assignment to placebo. While 65% of the effect of thrombolysis on PSD were caused directly, 35% were mediated by an improvement of the mRS. CONCLUSIONS: Treatment with alteplase in patients with acute stroke resulted in lower rates of depression at 90 days, which were only partially explained by reduced functional disability. Predictors of PSD including history and clinical characteristics may help in identifying patients at risk of PSD.

Metacognitive Training for Depression: Feasibility, safety and acceptability of two new treatment modules to reduce suicidality.

Recent evidence favours psychological interventions explicitly targeting suicidality; however, group treatments on suicidality are rare and are assumed to have unfavourable effects. We developed two modules specifically addressing suicidality that replace two existing modules in the Metacognitive Training for Depression (D-MCT). The aim of the current study was to examine the feasibility, safety, and acceptability of this intervention (D-MCT/S). Forty-eight inpatients with depression received eight sessions of D-MCT/S over 4 weeks in addition to standard treatment. Patients were assessed before the training, 4 and 8 weeks later regarding suicidality (primary outcome: Beck Suicide Scale [BSS]), hopelessness, depression (e.g. Hamilton Depression Rating Scale [HDRS]), dysfunctional attitudes, and self-esteem. Negative effects of the modules and subjective appraisal were assessed. Suicidality, hopelessness, and depression decreased over time. Whereas the effects on the BSS only reached trend level, a large effect was observed when the suicide item of the HDRS was used. Two of the 46 patients (4%) reported a deterioration in their symptoms, but this was not associated with the D-MCT/S. Negative effects of the general training were rather low, and acceptability was high. In general, patients evaluated the two new modules on suicidality similarly to the established modules. However, both modules were assessed as distressing by 39% of the patients. When we addressed suicidality in the D-MCT/S, we did not observe any contagious effects. In fact, the pilot versions of the two modules on suicidality are promising in terms of feasibility, safety, and acceptability. The results will be used to improve current shortcomings. The trial was registered with the German Clinical Trials Register (#DRKS-ID: DRKS00010543) on 23 August 2016.

Brief Web-Based Intervention for Depression: Randomized Controlled Trial on Behavioral Activation.

BACKGROUND: Web-based interventions have been shown to be effective for the treatment of depression. However, interventions are often complex and include a variety of elements, making it difficult to identify the most effective component(s). OBJECTIVE: The aim of this pilot study was to shed light on mechanisms in the online treatment of depression by comparing a single-module, fully automated intervention for depression (internet-based behavioral activation [iBA]) to a nonoverlapping active control intervention and a nonactive control group. METHODS: We assessed 104 people with at least mild depressive symptoms (Patient Health Questionnaire-9, >4) via the internet at baseline (t0) and 2 weeks (t1) and 4 weeks (t2) later. After the t0 assessment, participants were randomly allocated to one of three groups: (1) iBA (n=37), (2) active control using a brief internet-based mindfulness intervention (iMBI, n=32), or (3) care as usual (CAU, n=35). The primary outcome was improvement in depressive symptoms, as measured using the Patient Health Questionnaire-9. Secondary parameters included changes in activity, dysfunctional attitudes, and quality of life. RESULTS: While groups did not differ regarding the change in depression from t0 to t1 (ηp2=.007, P=.746) or t0 to t2 (ηp2=.008, P=.735), iBA was associated with a larger decrease in dysfunctional attitudes from t0 to t2 in comparison to CAU (ηp2=.053, P=.04) and a larger increase in activity from t0 to t1 than the pooled control groups (ηp2=.060, P=.02). A change in depression from t0 to t2 was mediated by a change in activity from t0 to t1. At t1, 22% (6/27) of the participants in the iBA group and 12% (3/25) of the participants in the iMBI group indicated that they did not use the intervention. CONCLUSIONS: Although we did not find support for the short-term efficacy of the single-module iBA regarding depression, long-term effects are still conceivable, potentially initiated by changes in secondary outcomes. Future studies should use a longer intervention and follow-up interval. TRIAL REGISTRATION: DKRS (#DRKS00011562).

Preoperative Depression and Plasma Cortisol Levels as Predictors of Delirium after Cardiac Surgery.

BACKGROUND: Delirium is common in old patients who undergo cardiac surgery, and it is associated with adverse outcomes. The genesis of delirium is thought to be multi-factorial, but it is still not well understood. Symptoms of depression and elevated cortisol level have been described in some previous studies as factors associated with delirium, suggesting a shared pathophysiology. AIMS: The objective of the present study was to determine whether preoperative depression symptoms and increased cortisol level represent risk factors for delirium after cardiac surgery. METHODS: We performed a prospective cohort study in 183 patients aged >50 years undergoing elective cardiac surgery. The Geriatric Depression Scale (GDS) was used to assess patients for depressive symptoms before surgery. Preoperative plasma cortisol levels were available in 145 participants. Delirium was diagnosed using the Confusion Assessment Method for Intensive Care Unit (CAM-ICU) during the first 7 days after surgery. Spearman correlation was used for correlations between GDS, Mini-Mental State Examination (MMSE), Charlson comorbidity index, and age. Binary logistic regression was used to determine whether GDS and cortisol levels predict postoperative delirium. RESULTS: Delirium occurred in 60 patients out of 183 (32.8%) included and lasted 2.3 days (SD 1.36). GDS was correlated with age (p = 0.001) and comorbidity index (p = 0.003) and inversely correlated with MMSE score (p < 0.001). Higher preoperative GDS scores were associated with incidence of delirium in the postoperative period (p = 0.002). The association was significant after controlling for age, MMSE score, history of stroke, and Charlson comorbidity index (p = 0.045). Preoperative cortisol level was not associated with the development of postoperative delirium. CONCLUSION: Our results suggest that a higher preoperative depression score is associated with an increased risk of postoperative delirium. On the other hand, preoperative plasma cortisol level does not seem to be a predictor of delirium after surgery. Further studies are needed to determine the potential of preoperative depression treatment to prevent postoperative delirium.

Metacognitive Training for Depression (D-MCT) reduces false memories in depression. A randomized controlled trial.

Metacognitive Training for Depression (D-MCT) is a highly standardized group program targeted at depression-related ("Beckian") emotional as well as cognitive biases, including mood-congruent and false memory. While prior results are promising with respect to psychopathological outcomes (depression), it is unclear whether D-MCT also meets its goal of improving cognitive biases, such as false memories. In the framework of a randomized controlled trial (registered trial, DRKS00007907), we investigated whether D-MCT is superior to an active control condition (health training, HT) in reducing the susceptibility of depressed patients for false memories. False memories were examined using parallel versions of a visual variant of the Deese-Roediger McDermott paradigm. Both groups committed less false memories at post assessment after 4 weeks compared to baseline. Relative to HT, D-MCT led to a significant decrease in high-confident false memories over time. The study presents first evidence that D-MCT decreases the susceptibility of depressed patients for false memories, particularly for errors made with high confidence that are presumably the most "toxic" in terms of mood-congruent memory distortions.

Are we exaggerating neuropsychological impairment in depression? Reopening a closed chapter.

BACKGROUND: Meta-analyses conclude that individuals with depression display neurocognitive deficits. However, the extent to which some of these impairments occur due to secondary influences, and thus in part represent epiphenomena, has rarely been tested. Therefore, the authors examined the impact of performance motivation, attitude towards cognitive assessment, and momentary symptoms during assessment on neuropsychological test results in depression. RESEARCH DESIGN AND METHODS: Forty-five patients with depression and 60 nonclinical individuals underwent a comprehensive neuropsychological test battery. Before and after the assessment, each participant was asked to complete the Momentary Influences, Attitudes and Motivation Impact on Cognitive Performance Scale (MIAMI). RESULTS: As hypothesized, patients with depression performed worse than nonclinical controls on most neuropsychological parameters. Group differences achieved a medium effect size for parameters tapping speed and a large effect for parameters tapping accuracy. Yet, only one fourth of the patient population displayed abnormal scores (≥ 1 SD below the population mean). In line with the hypothesis, patients with depression were more fearful of test outcomes, complained more about negative momentary influences, and were less motivated (based on retrospective assessment) than controls, as assessed with the MIAMI. The MIAMI total score mediated the relationship between group status and test scores in three out of four analyses. When MIAMI scores were entered as covariate, group differences were largely reduced. DISCUSSION: Patients with depression show a more negative attitude towards testing, lower performance motivation, and more negative momentary influences, all of which induce malperformance. The results suggest that performance dysfunction does not necessarily mirror brain dysfunction in areas hosting cognitive functions but is confounded with other factors. Greater caution is warranted when interpreting the results of neuropsychological tests in depressed patients.

Amyloid-ß Precursor Protein Modulates the Sorting of Testican-1 and Contributes to Its Accumulation in Brain Tissue and Cerebrospinal Fluid from Patients with Alzheimer Disease.

The mechanisms leading to amyloid-ß (Aß) accumulation in sporadic Alzheimer disease (AD) are unknown but both increased production or impaired clearance likely contribute to aggregation. To understand the potential roles of the extracellular matrix proteoglycan Testican-1 in the pathophysiology of AD, we used samples from AD patients and controls and an in vitro approach. Protein expression analysis showed increased levels of Testican-1 in frontal and temporal cortex of AD patients; histological analysis showed that Testican-1 accumulates and co-aggregates with Aß plaques in the frontal, temporal and entorhinal cortices of AD patients. Proteomic analysis identified 10 fragments of Testican-1 in cerebrospinal fluid (CSF) from AD patients. HEK293T cells expressing human wild type or mutant Aß precursor protein (APP) were transfected with Testican-1. The co-expression of both proteins modified the sorting of Testican-1 into the endocytic pathway leading to its transient accumulation in Golgi, which seemed to affect APP processing, as indicated by reduced Aß40 and Aß42 levels in APP mutant cells. In conclusion, patient data reflect a clearance impairment that may favor Aß accumulation in AD brains and our in vitro model supports the notion that the interaction between APP and Testican-1 may be a key step in the production and aggregation of Aß species.

Effects of online intervention for depression on mood and positive symptoms in schizophrenia.

BACKGROUND: Depression is common in schizophrenia. Whereas the improvement of mood and self-esteem represents a subjective treatment priority for many patients, depression is rarely a primary target for clinical intervention. The present trial examined whether an online intervention for depression can ameliorate depressive symptoms in schizophrenia. METHODS: A total of 58 individuals with schizophrenia were invited to participate in an online survey which encompassed the Center for Epidemiologic Studies-Depression Scale (CES-D, primary outcome), the Patient-Health-Questionnaire-9 (PHQ-9) and the Paranoia Checklist. Subsequently, telephone interviews were conducted to verify diagnostic status and assess symptoms (Positive and Negative Syndrome Scale, PANSS). Participants were randomized either to the experimental condition (online depression intervention) or to a waitlist control condition. Three months after inclusion, a reassessment was carried out (self-report and telephone interview blind for group condition). The trial was registered (registration: DRKS00007888). RESULTS: Participants in the treatment group showed a significant decline of depressive symptoms at a medium-to-large effect size, as assessed with the CES-D and the PANSS depression item, in comparison to the waitlist control group (completer (CC) and intention-to-treat analyses (ITT)). For the PHQ-9 (CC and ITT) and the PANSS distress subscale (CC only) significance was bordered at a medium effect size. Completion at the post-assessment after three months was 84%. DISCUSSION: Depression in schizophrenia is both underdiagnosed and undertreated. To reduce the large treatment gap in the disorder, low threshold strategies are urgently needed. Online treatment and bibliotherapy may represent valuable tools to address patients' needs beyond the treatment of the core positive syndrome.

MicroRNA Profiling of CSF Reveals Potential Biomarkers to Detect Alzheimer`s Disease.

The miRBase-21 database currently lists 1881 microRNA (miRNA) precursors and 2585 unique mature human miRNAs. Since their discovery, miRNAs have proved to present a new level of epigenetic post-transcriptional control of protein synthesis. Initial results point to a possible involvement of miRNA in Alzheimer's disease (AD). We applied OpenArray technology to profile the expression of 1178 unique miRNAs in cerebrospinal fluid (CSF) samples of AD patients (n = 22) and controls (n = 28). Using a Cq of 34 as cut-off, we identified positive signals for 441 miRNAs, while 729 miRNAs could not be detected, indicating that at least 37% of miRNAs are present in the brain. We found 74 miRNAs being down- and 74 miRNAs being up-regulated in AD using a 1.5 fold change threshold. By applying the new explorative "Measure of relevance" method, 6 reliable and 9 informative biomarkers were identified. Confirmatory MANCOVA revealed reliable miR-100, miR-146a and miR-1274a as differentially expressed in AD reaching Bonferroni corrected significance. MANCOVA also confirmed differential expression of informative miR-103, miR-375, miR-505#, miR-708, miR-4467, miR-219, miR-296, miR-766 and miR-3622b-3p. Discrimination analysis using a combination of miR-100, miR-103 and miR-375 was able to detect AD in CSF by positively classifying controls and AD cases with 96.4% and 95.5% accuracy, respectively. Referring to the Ingenuity database we could identify a set of AD associated genes that are targeted by these miRNAs. Highly predicted targets included genes involved in the regulation of tau and amyloid pathways in AD like MAPT, BACE1 and mTOR.

Association between fully automated MRI-based volumetry of different brain regions and neuropsychological test performance in patients with amnestic mild cognitive impairment and Alzheimer's disease.

Fully automated magnetic resonance imaging (MRI)-based volumetry may serve as biomarker for the diagnosis in patients with mild cognitive impairment (MCI) or dementia. We aimed at investigating the relation between fully automated MRI-based volumetric measures and neuropsychological test performance in amnestic MCI and patients with mild dementia due to Alzheimer's disease (AD) in a cross-sectional and longitudinal study. In order to assess a possible prognostic value of fully automated MRI-based volumetry for future cognitive performance, the rate of change of neuropsychological test performance over time was also tested for its correlation with fully automated MRI-based volumetry at baseline. In 50 subjects, 18 with amnestic MCI, 21 with mild AD, and 11 controls, neuropsychological testing and T1-weighted MRI were performed at baseline and at a mean follow-up interval of 2.1 ± 0.5 years (n = 19). Fully automated MRI volumetry of the grey matter volume (GMV) was performed using a combined stereotactic normalisation and segmentation approach as provided by SPM8 and a set of pre-defined binary lobe masks. Left and right hippocampus masks were derived from probabilistic cytoarchitectonic maps. Volumes of the inner and outer liquor space were also determined automatically from the MRI. Pearson's test was used for the correlation analyses. Left hippocampal GMV was significantly correlated with performance in memory tasks, and left temporal GMV was related to performance in language tasks. Bilateral frontal, parietal and occipital GMVs were correlated to performance in neuropsychological tests comprising multiple domains. Rate of GMV change in the left hippocampus was correlated with decline of performance in the Boston Naming Test (BNT), Mini-Mental Status Examination, and trail making test B (TMT-B). The decrease of BNT and TMT-A performance over time correlated with the loss of grey matter in multiple brain regions. We conclude that fully automated MRI-based volumetry allows detection of regional grey matter volume loss that correlates with neuropsychological performance in patients with amnestic MCI or mild AD. Because of the high level of automation, MRI-based volumetry may easily be integrated into clinical routine to complement the current diagnostic procedure.

Genetic risk factors for depression in Alzheimer`s disease patients.

OBJECTIVE: Alzheimer's Disease (AD) is often associated with depressive symptoms developing at any time before and after AD onset. The aetiology of depression in AD has not sufficiently been characterized, but biological aspects due to neurodegeneration and/ or genetic risk factors may play a plausible role and may distinguish it from common depressive disorders. METHOD: To investigate the possible relationship between genetic risk factors and depression in AD, we assessed genetic polymorphisms reported to be associated with depression (MAOA VNTR, ACE 288bp Insertion/ Deletion, 5HTTLPR, COMT Val158Met, BDNF Val66Met, TPH1 A218C, HTR2A T102C, P2RX7 Q460R, FKBP5 rs1360780 and CRHR1 rs242941) in a cross-sectional study on 246 AD patients with or without clinically significant major depressive disorder (MDD) according to DSM-IV. RESULTS: Significant associations between AD and MDD have been found for three polymorphisms mainly in females (TPH1 A218C, MAOA VNTR and BDNF Val66Met) and one polymorphism in the total population only (FKBP5 rs1360780). There was an increased risk of having MDD in homozygous female carriers of the TPH1 A-allele (odds ratio: 4.35) and homozygous carriers of the MAOA VNTR low activity allele 3R (odds ratio: 3.37). CONCLUSION: We detected allelic or genotypic associations of MAOA, TPH1, FKBP5 and BDNF in clinically significant MDD in AD. Odds-ratios were generally higher in female AD-patients, which might be due to the composition of the study population. Further studies on the neurotransmitter systems affected by the genetic polymorphisms found to be associated with MDD in AD may help to elucidate the underlying pathomechanisms of MDD.

Non-Alzheimer's disease-related memory impairment and dementia.

Although Alzheimer's disease (AD) is a common cause of memory impairment and dementia in the elderly disturbed memory function is a widespread subjective and/or objective symptom in a variety of medical conditions. The early detection and correct distinction of AD from non-AD memory impairment is critically important to detect possibly treatable and reversible underlying causes. In the context of clinical research, it is crucial to correctly distinguish between AD or non-AD memory impairment in order to build homogenous study populations for the assessment of new therapeutic possibilities. The distinction of AD from non-AD memory impairment may be difficult, especially in mildly affected patients, due to an overlap of clinical symptoms and biomarker alterations between AD and certain non-AD conditions. This review aims to describe recent aspects of the differential diagnosis of AD and non-AD related memory impairment and how these may be considered in the presence of memory deficits.

Aunque la Enfermedad de Alzheimer (EA) constituye una causa común de demencía y deterioro de memoria en la vejez, el trastorno de memoria es un síntoma generalizado objetivo ylo subjetivo en una variedad de situaciones médicas. La detección precoz y la correcta distinción entre la EA y el deterioro de memoria no-EA es muy importante para determinar causas subyacentes posiblemente tratables y reversibles. En el contexto de la investigation clínica es clave distinguir correctamente entre EA y deterioro de memoria no-EA para conformar poblaciones homogéneas de estudio para la evaluación de nuevas alternativas terapéuticas. La distinción entre EA y deterioro de memoria no-EA puede resultar difícíl, especialmente en pacientes con compromise leve, debido a una sobreposición de sintomas clínicos y alteraciones de biomarcadores entre la EA y ciertas condiciones no-EA. Esta revisóon tiene como objetivo describir aspectos recientes del diagnóstico diferencial de la EA y del deterioro de memoria no relacionado con la EA, y cómo estos pueden considerarse cuando hay presencia de déficit de memoria.

La maladie d'Alzheimer (MA) est une cause fréquente de troubles de la mémoire et de démence chez les sujets âgés mais une fonction mnésique perturbée est un symptôme subjectif et/ou objectif très répandu dans de nombreuses pathologies. La détection précoce et une distinction correcte entre troubles mnésiques lies ou non à la MA sont primordiales pour diagnostiquer des causes sous-jacentes qui pourraient être réversibles et traitables. En recherche clinique, faire cette distinction est essentiel pour constituer des populations d'étude homogènes afin d'évaluer de nouveaux traitements. La superposition des symptômes cliniques et des modifications des biomarqueurs entre la MA et d'autres pathologies non-MA peut rendre difficile la différentiation selon I'étiologie, surtout chez les patients légèrement atteints. Dans cet article nous décrivons les caractéristiques récentes du diagnostic différentiel entre troubles mnésiques liés ou non à la MA et leur prise en compte en présence d'un déficit de la mémoire.

Prevention and treatment options for postoperative delirium in the elderly.

PURPOSE OF REVIEW: To review recent findings and developments in strategies for prevention and treatment of postoperative delirium. RECENT FINDINGS: Current advances in the field include improved knowledge about predisposing and precipitating factors, evidence for efficacy of multicomponent prevention programmes, refinement of perioperative procedures, and promising pharmacological approaches for prophylaxis and management of postoperative delirium. SUMMARY: Postoperative delirium is a common and serious complication in elderly patients. Preoperative assessment of risk profiles and tailored multimodal prevention approaches proved effective and should be integrated into clinical practice. Despite promising recent findings, at present, the routine use of pharmacological prophylaxis cannot be recommended. Validated and easy-to-use bedside diagnostic tools are available and should be regularly applied for delirium screening in the first days after surgery. In patients developing delirium, causal conditions and contributing factors need to be identified and addressed. Whereas administration of antipsychotics may represent an option for symptomatic treatment, further studies are needed to evaluate the effects of pharmacological approaches on long-term outcomes in elderly patients with delirium.

Effect of one-year vitamin C- and E-supplementation on cerebrospinal fluid oxidation parameters and clinical course in Alzheimer's disease.

Antioxidant vitamins are being widely discussed as a therapeutic option in Alzheimer's disease (AD). We recently found that supplementation with vitamin C and E over 1 month leads to an increase of their levels in cerebrospinal fluid (CSF) and a reduction of CSF lipid peroxidation. In the present study, we followed-up the biochemical and clinical effect of vitamin C and E supplementation in an open clinical trial over 1 year. Twelve AD patients stably taking a cholinesterase inhibitor were supplemented with vitamin C (1,000 mg/day) and E (400 I.U./day), while 11 patients taking cholinergic medication only served as a control group. Cognition was assessed at baseline, after 6 months and 12 months using the Mini-Mental State Examination; a more detailed testing of cognitive function was performed at baseline and after 12 months. From eight of the vitamin-supplemented patients, CSF was taken at baseline, after 1 month and after 1 year to measure the antioxidant effect of vitamin supplementation on CSF lipids using a recently established in vitro oxidation assay. CSF antioxidant vitamins were significantly increased after 1 month and 1 year of supplementation, while in vitro oxidation of CSF lipids was significantly reduced only after 1 year of the supplementation. The clinical course of AD did not significantly differ between the vitamin and the control group. We conclude that supplementation with vitamins E and C did not have a significant effect on the course of AD over 1 year despite of a limited antioxidant effect that could be observed in CSF.

Dimethylarginines, homocysteine metabolism, and cerebrospinal fluid markers for Alzheimer's disease.

Dimethylarginine and homocysteine metabolism are closely linked and alterations of both were observed in plasma and cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD). CSF parameters of homocysteine metabolism have recently been found to be associated with the CSF level of the AD biomarker phosphorylated tau (ptau) in AD patients. To investigate possible relationships between homocysteine and dimethylarginine metabolism and the AD CSF biomarkers ptau181 and amyloid-ß 1-42 (Aß42), we assessed parameters of homocysteine metabolism (CSF homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), 5-methyltetrahydrofolate (5-MTHF)) and dimethylarginine metabolism (plasma and CSF asymmetric dimethylarginine (ADMA), symmetric dimethylarginine, L-arginine) as well as CSF Aß42 and ptau181 in 98 controls and 51 AD patients. Multivariate linear regression analyses were performed to assess associations between the considered parameters. SAH concentrations show significant associations to CSF ADMA levels, and CSF ADMA and L-arginine to ptau181, but not to Aß42 concentrations in AD patients. When including concentrations of homocysteine, 5-MTHF, SAM, and SAH into the analysis, CSF ADMA concentrations independently predicted ptau181 levels in AD patients but homocysteine-related metabolites were associated with ptau181 only when ADMA was removed from the analysis model. These results suggest that CSF ADMA may interact with CNS homocysteine metabolism and may contribute to neurodegeneration and accumulation of phosphorylated tau in AD. Functional and interventional studies are needed to further proof this hypothesis.